JP2020500632A - Inhaler - Google Patents

Abstract

An inhalation device for delivering a medicament to a user may include a mouthpiece, a dosing chamber, and a flow path connecting the mouthpiece to the dosing chamber. The dosing chamber may be configured to deliver the medicament to the user via the mouthpiece. The inhalation device may include a motorized oscillating element, a sensor system configured to generate a pressure signal indicative of airflow through the flow path, and a controller. The controller may be configured to receive a pressure signal from a sensor system (eg, a micro-electro-mechanical (MEMS) pressure sensor). The controller may be configured to perform an inhalation detection procedure to determine a plurality of successful inhalations. For example, the controller may be configured to generate a trigger signal to control the timing of the operation of the electrically powered oscillating element based on the plurality of successful inhalations to release the medicament into the dosing chamber. [Selection diagram] FIG. 1A

Description

Cross-reference of related applications

  This application claims the benefit of US Provisional Patent Application No. 62 / 432,237, filed December 9, 2016, the disclosure of which is incorporated herein by reference in its entirety.

  Metered dose inhalers (MDIs), dry powder inhalers, jet nebulizers, and ultrasonic nebulizers are drug delivery systems for treating respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). The MDI may utilize a "press and breath" drug delivery mechanism whereby a user presses a canister to release a dose of aerosolized drug and from a mouthpiece on the device. Inhale the drug. To ensure that the entire dose of drug is received, the MDI may require the user to time the release of the drug from the inhaler with his own inhalation. Therefore, the MDI may be erroneously operated when the user cannot properly and consistently adjust the inhalation timing when pressing the medicine canister.

  Other types of inhalers, such as dry powder inhalers, may be breath actuated and provide sufficient drug in the device to activate the drug delivery mechanism and allow the user to receive the drug. The generation of a good airflow may depend on the ability of the user. If the user's inhalation is too weak, the device may not be able to aerosolize the full dose of the drug. Thus, if a user has limited lung capacity and / or function, the ability of a breath-actuated inhaler to deliver an appropriate dose of medication may be compromised.

  The jet nebulizer allows a user to receive medication using his or her own normal breathing pattern, and thus can deliver medication without the need for forced inhalation. However, jet nebulizers are often inefficient. The device may spray more medicament than can be inhaled during a single inspiratory effort. Thus, a significant portion of the nebulized medication may be lost during the expiratory cycle of the user's breathing pattern.

  An inhalation device for delivering a medicament to a user may include a mouthpiece, a dosing chamber, and a flow path connecting the mouthpiece to the dosing chamber. The dosing chamber may be configured to deliver the medicament to the user via the mouthpiece. The inhaler may include a motorized oscillating element, a sensor system configured to generate a pressure signal indicative of airflow through the flow path, and a controller. The controller may be configured to receive the pressure signal from the sensor system. The sensor system may include an atmospheric pressure sensor (eg, a micro-electro-mechanical (MEMS) pressure sensor) and / or a differential pressure sensor. The pressure signal may include an absolute air pressure measurement. The controller may be further configured to generate a flow signal using the pressure signal, wherein the flow signal is an average output of the pressure signal. The controller determines the atmospheric pressure continuously using the pressure signal during periods of no user activity (e.g., between breaths), determines the average atmospheric pressure over time, and stores the average atmospheric pressure in memory. It may be configured to do so.

  The controller may be configured to perform an inhalation detection procedure to determine a plurality of successful inhalations. The controller may be configured to activate and deactivate the vibrating element. For example, the controller is configured to generate a trigger signal to control the timing of the operation of the electrically powered oscillating element based on the plurality of successful inhalations to release the medicament into the dosing chamber and toward the patient. You may.

  For example, the controller determines whether the slope of the first cycle of the flow signal is above a predetermined slope threshold, and activates if the slope of the first cycle of the flow signal is above the predetermined slope threshold. It is configured as follows. The controller may be configured to start a timer when it becomes active. In operation, the controller uses the first cycle of the flow signal to calculate the suction volume (volume of air passing through the flow path) and determine that the first cycle suction volume exceeds the suction volume threshold. And determining that the pressure measurement in the first cycle of the flow signal has returned to within the atmospheric pressure threshold, determining that the slope of the second cycle of the flow signal has exceeded a predetermined slope threshold, It is determined that the pressure measurement of the second cycle of the flow signal has exceeded the pressure threshold, and the slope of the second cycle of the flow signal exceeding the predetermined slope threshold and the flow exceeding the predetermined slope threshold. A trigger signal is generated based on the pressure measurement of the second cycle of the signal and the motorized vibration element is configured to cause release of the medicament into the dosing chamber and toward the patient. To have. The controller may be configured to exit the activation state if the suction volume does not exceed the suction volume threshold or if the suction gradient does not exceed the predetermined gradient threshold.

  The controller confirms user inhalation using the first cycle of the flow signal, advances the blister pack containing the dose of medication using the second cycle of the flow signal, and uses the third cycle of the flow signal. The cycle may be used to generate a trigger signal to cause the motorized oscillating element to release a dose of medicament from the blister pack into the dosing chamber. The controller confirms the user inhalation, advances the blister pack containing the dose of medicament using the first cycle of the flow signal, and generates a trigger signal using the second cycle of the flow signal; The electric vibration element may be configured to release one dose of the medicine from the blister pack into the administration chamber.

  FIG. 1A is a front perspective view of an example of the inhaler.

  FIG. 1B is a side perspective view of an example of the inhaler shown in FIG. 1A.

  FIG. 2 is a block diagram of an example of the inhaler.

  FIG. 3 is an internal perspective view of an example of the inhaler.

  FIG. 4 is a diagram illustrating an example of a pressure signal received by the control circuit from the inhaler.

  FIG. 5 is a diagram of an example of a system including an inhaler.

  FIG. 6 is a flowchart illustrating an example of an inhalation detection procedure performed by the inhaler.

[Detailed description]
The present disclosure describes instruments, systems, and methods for inhalation devices. The inhalation device may activate the release of the drug based on the user's breathing pattern, and the breathing pattern may be a natural inspiration and expiration pattern. The drug may be in the form of a dry powder stored on a blister strip. Each dose of the dry powder medicament may be stored in a specific blister within the blister strip. The inhalation device may be referred to as a tidal inhaler and may be configured to coordinate the release of the drug during inhalation by the user such that at least a substantial portion of the released drug is inhaled during inhalation. . Accordingly, the inhalation device may be configured to efficiently deliver medication to a user while reducing or eliminating user errors that may be associated with other devices such as MDIs.

  FIG. 1A is a front perspective view of an example of the inhaler 100. FIG. FIG. 1B is a side perspective view of an example of the inhaler 100 shown in FIG. 1A. Inhalation device 100 may be an active dry powder inhaler. The inhaler 100 may include a plurality of periodic breaths (eg, continuous inhalation and exhalation to the inhaler 100) and / or “pipe smoking” breaths (eg, continuous inhalation through the inhaler 100, and the device 100). Exhalation from the user's mouth away from the mouth) may provide a breath-activated medication of the drug. The inhalation device 100 may include a main body 102 and a drug cartridge 104. The body 102 may be coupled to the drug cartridge 104, for example, such that the drug cartridge 104 can be removed from the body 102 and replaced. The drug cartridge 104 may include multiple doses of the drug (eg, 30 doses). The medicine cartridge 104 may be removed and replaced when the medicine is used up, or a new medicine cartridge may be attached to the main body 102 of the inhalation device 100. Accordingly, the main body 102 may be used with a plurality of drug cartridges 104.

  The main body 102 may include one or more of the internal components of the inhalation device 100. For example, body 102 may include control circuitry, memory, communication circuitry, user interface, and / or power for inhalation device 100. The main body 102 may include a power button 108 for a user to turn on / off the inhaler 100. The main body 102 includes a power and / or data port 116 that can be used to charge the power supply of the inhaler 100, transfer data to and / or transfer data from the inhaler 100. Is also good. Body 102 may also include additional power and / or data ports (not shown) opposite power and / or data ports 116 (eg, using port 116 for data). However, other ports opposite port 116 may be used for power, or vice versa). The main body 102 may include a graphical user interface 106 for presenting information via the medicament cartridge 104 when the main body 102 and the medicament cartridge 104 are coupled. The body 102 may include, for example, a release mechanism 112 used to release the drug cartridge 104 from the body 102 when the drug cartridge 104 uses up the drug.

  Drug cartridge 104 may include a mouthpiece 114. The drug cartridge 104 may further include a suction / discharge port 110, which may be configured to provide airflow between the mouthpiece 114 and the suction / discharge port 110 (the drug cartridge 104 (a drug stored therein). )). Thus, when the user inhales through the mouthpiece 114, air flows into the port 110, and when the user exhales through the mouthpiece 114, air flows out of the port 110. As a result, the inhaler 100 can operate as a tidal inhaler, in which case the user performs inhalation through the inhaler 100 and exhalation into the inhaler 100 to receive the drug. Also, the inhaler 100 can operate as a "pipe" inhaler, in which the user inhales through the inhaler 100 but exhales the mouthpiece away from the mouth. For example, the inhalation device 100 (e.g., the drug cartridge 104) allows the user to inhale through the suction / exhalation port 110 and the mouthpiece 114, and exhales the user through the mouthpiece 114 and the suction / exhalation port 110. May be included. In one or more examples, the inhaler 100 may be configured to operate as a tidal inhaler or as a pipe inhaler, for example, by setting the operation of a one-way valve. Finally, the body 102 may include a recess for receiving the suction / discharge port 110, for example, as shown in FIGS. 1A-1B.

  FIG. 2 is a block diagram of an example of the inhaler 200. Inhaler 200 may be an example of inhaler 100 of FIGS. 1A-B. The inhalation device 200 may include a control circuit 201, a memory 202, a power supply 203, a communication circuit 204, a sensor system 205, a user interface 206, a blister strip advance mechanism 207, a drug cartridge interface 208, and a vibration element 209. The control circuit 201 may be a processor (eg, a microprocessor), a microcontroller, a programmable logic device (PLD), a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), or any suitable controller or processing device. One or more of them may be included.

  The control circuit 201 may be configured to control the operation of one or more components of the inhalation device 200. For example, the control circuit 201 may be configured to receive a pressure signal from the sensor system 205. The control circuit 201 may be configured to activate and deactivate the vibration element 209. The control circuit 201 may be configured to execute an inhalation detection procedure (e.g., the inhalation detection procedure 500) for determining a plurality of successful inhalations. The control circuit 201 controls the timing of the operation of the electric vibration element 209 to release the medicament into the dosing chamber of the inhalation device 200 and to the patient based on the plurality of successful inhalations. It may be configured to generate a trigger signal.

The memory 202 may be communicably connected to the control circuit 201, for example, for storing and / or retrieving operation settings of the inhaler 200, sensor data, and the like. The memory 202 may be realized as an external IC (Integrated Circuit), or may be realized as an internal circuit of the control circuit 201. The power supply 203 may generate a direct current (DC) supply voltage Vcc for supplying power to the control circuit 201 and other low voltage circuits or high voltage circuits (for example, the vibrating element 209) of the inhaler 200. The communication circuit 204 may include a wired and / or wireless communication circuit. Communication circuit 204 may be used to transmit and / or receive radio frequency (RF) signals, for example, via an antenna (not shown). The wireless communication circuit 204 may include, for example, an RF receiver, an RF transmitter, and / or an RF transceiver. Communication line 204, Wi-Fi, Bluetooth ^{(registered trademark)} (e.g., Bluetooth Low Energy), ZIGBEE ^{(registered trademark),} may be transmitted via the dedicated communication protocols and / or other proprietary protocols such as Thread .

  Sensor system 205 may include one or more atmospheric pressure sensors, such as a micro-electro-mechanical (MEMS) pressure sensor. Although MEMS pressure sensors can provide small and low cost sensors, some MEMS pressure sensors can be "noisy." For this reason, the inhalation device 200 performs a plurality of calculations using the pressure signal received from the sensor system 205, as described with reference to FIGS. It may be accurately determined whether or not breathing is performed. Alternatively or additionally, sensor system 205 may include one or more differential pressure sensors.

  At least a portion of the sensor system 205 may be in fluid communication with the flow path between the mouthpiece and the suction / discharge port of the inhalation device 200. For example, the sensor system 205 may be located within the body of the inhalation device and may be in fluid communication with the flow path between the mouthpiece and the suction / discharge port of the drug cartridge. For example, the body may include a port (e.g., port 318) and the drug cartridge may include a port (e.g., port 316) that exists between the mouthpiece and the suction / exhalation of the drug cartridge. . The combination of the body port and the drug cartridge port can provide fluid communication between the sensor system 205 and the flow path. Alternatively or additionally, the sensor system 205 may be in fluid communication by using a tube connected to the sensor system 205 and the flow path of the drug cartridge.

  Sensor system 205 may be configured to generate a pressure signal indicative of airflow through the flow path of inhalation device 200. Sensor system 205 can provide a pressure signal to control circuit 201. The pressure signal may include absolute pneumatic pressure measurements and / or unfiltered pressure measurements (eg, gauge pressure). In some embodiments, the sensor system 205 comprises one or more pressure sensors used to measure pressure in the flow path of the inhalation device, and one or more pressure sensors dedicated to measuring atmospheric pressure. May be included.

  User interface 206 may include a display (eg, graphical user interface 106) and one or more actuators (eg, power button 108). The display may include, for example, a liquid crystal display (LCD) screen. The display may be backlit by one or more light sources (eg, white backlight LEDs). The display may include, for example, medication information (eg, medication reminders, medication completion / incomplete signatures, medication progress signs, medication counters, etc.), medication cartridge information (eg, medication, remaining dose, expiration date, medication cartridge attachment message, etc.), battery It may be configured to display patient feedback information and / or operating characteristics of the inhalation device 200, such as charge level, communication and data transfer information.

  Inhalation device 200 may include one or more indicators, such as a light emitting diode (LED) 210 or an organic LED (OLED) screen. LED 210 may include a plurality of LEDs of different colors. The control circuit 201 may be configured to notify the user of information by operating the LED 210 (for example, lighting, blinking, and the like). For example, the control circuit 201 may notify that the inhalation has been detected by lighting an LED of a specific color (for example, blue). The control circuit 201 may notify that the medication is completed by lighting an LED of another color (for example, green). The control circuit may indicate that there is an error by lighting an LED of another color (for example, orange). The control circuit may indicate the status of the inhalation device 200 by operating the LED and / or indicate a particular operation of the device 200 (eg, illuminate or flash the LED when the vibrating element 209 is activated). Let it do). In some examples, the control circuit 200 may turn on (or blink, etc.) the LED as a signal to the user to draw, and stop turning on the LED when the medication is completed and the user finishes drawing.

  Inhalation device 200 may include a medicament packaged in a blister strip. Accordingly, the blister strip advancement mechanism 207 of the inhalation device 200 may be configured to advance the blister strip to prepare a dose of medicament for delivery to a patient. For example, a blister strip may include a plurality of blisters (eg, dimples) sealed with a cover (eg, a piece of aluminum, paper, and / or plastic), wherein one or more blisters are For one dose of medicine. The blister strip advancement mechanism 207 may be configured to remove the cover to expose the medicament in the blister and move the blister to a position for delivery to a user. As described in more detail herein, the blister strip advancement mechanism 207 may move the blister to a position adjacent the dosing chamber and / or the vibrating element 209. The vibrating element 209 vibrates and / or acoustically levitates the medicament from the blister into the dosing chamber of the inhalation device 200 such that the medicament reaches the flow path through the dosing chamber nozzle and is inhaled by the user. You may be comprised so that it may face. The vibration element 209 may include, for example, a piezoelectric transducer.

  The drug cartridge interface 208 may be mechanical and / or electrical in nature. The drug cartridge interface 208 may be configured to form a secure connection between the body of the inhalation device 200 and the drug cartridge (eg, the body 102 of the inhalation device 100 and the drug cartridge 104). The drug cartridge interface 208 may include a sensor that provides a signal to the control circuit 201 indicating that the drug cartridge is properly connected to the body of the inhalation device 200. The medicine cartridge interface 208 may include an internal memory, and may store cartridge information such as, for example, medication information (for example, the remaining number of medications).

  FIG. 3 is an internal perspective view of an example of the inhalation device 300. Inhaler 300 may be an example of inhaler 100 and / or inhaler 200. The inhalation device includes a vibrating element 302, a blister 304, a drug 305, a dosing chamber 306, a flow path 308 between the inhalation device mouthpiece 314 and the suction / exhalation port 310, a sensor system 312 and / or one or more dosing chambers. A nozzle 320 may be included. Air can enter through the inlet / outlet port 310, exit the mouthpiece of the inhaler through the flow path 308, and vice versa. The vibration element 302 may include a piezoelectric transducer.

  Inhalation device 300 may include a main body and a drug cartridge. The body may include the sensor system 312 and the vibration element 302. The medication cartridge may include a mouthpiece 314, blister 304, medication 305, medication chamber 306 and one or more medication chamber nozzles 320, suction / discharge port 310 and flow channel 308. In FIG. 3, different hash types are used to help distinguish between the body of the inhalation device 300 and the drug cartridge.

  The sensor system 312 may be the whole sensor system or a part of the whole sensor system. The sensor system 312 may be placed in fluid communication with the flow path 308, such that, for example, the sensor 312 generates a signal indicative of airflow through the flow path 308. For example, a drug cartridge may include a port 316 (eg, a hole) and the body may also include a port 318 (eg, a hole). Ports 316 and 318 provide fluid communication between sensor system 312 and flow path 308. The sensor system 312 can provide a pressure signal to a control circuit (not shown) of the inhalation device 300, for example, to indicate when a user has inhaled and / or exhaled via the inhalation device 300. It may be used to determine. For example, the inlet / outlet port 310 creates a restriction that will define a known resistance to airflow through the flow path that is used to determine pressure changes in the flow path. The pressure change may be detected by the sensor system 312 and output as a pressure signal.

  The control circuit of the inhalation device 300 may, for example, determine whether to deliver a medicament to a user, as described in more detail herein. The control circuit may prepare a dose of medication present in the blister for delivery to the patient, for example, by advancing a blister pack of medication through a blister strip advancement mechanism. When the blister 304 is located below the dosing chamber 306 (eg, next to the vibrating element 302), the control circuit controls the timing of operation of the vibrating element 302 by generating a trigger signal, and 305 may be released. For example, the vibrating element 302 may vibrate and agitate the sidewalls of the dosing chamber 306, which may push the medication 305 out of the blister 304. The vibrating element 302 may acoustically excite the dosing chamber 306, thereby inducing a synthetic jet on each side of the dosing chamber nozzle 314, for example. The internal jet mixes or agitates the medicament 305 within the dosing chamber 306 and allows the external jet to transport the medicament 305 to the mouthpiece 314 of the inhaler 300 via the dosing chamber nozzle 320 and the flow path 308. Good. Thus, the control circuit may time the operation of the vibrating element 302 such that the vibrating element 302 causes the release of the medicament 305 into the dosing chamber 306 while the user is inhaling through the mouthpiece 314. .

  FIG. 4 is a diagram 400 of an example of a signal determined by a control circuit of an inhaler (eg, inhaler 100, inhaler 200 and / or inhaler 300) using a pressure signal received from the sensor system of the inhaler. is there. The diagram 400 may include a flow signal 402, a rate of pressure change (eg, gradient) signal 404, a volume signal 406, and a signal 408 indicative of the condition of the inhaler.

  The sensor system may generate a raw pressure signal (not shown) and provide the raw pressure signal to a control circuit of the inhaler. The raw pressure signal may be an absolute pressure (eg, in Pascal). The control circuit may receive a raw pressure signal from the sensor system. The control circuit may also use the raw pressure signal to determine an atmospheric pressure level (not shown) during periods of inactivity (eg, when the user is not inhaling or exhaling the device). Good. For example, the control circuit may determine the atmospheric pressure by averaging the raw pressure signal over time, applying a low pass filter to the raw pressure signal, or a similar technique. The control circuit may determine the atmospheric pressure continuously, or may determine the atmospheric pressure after determining that the gradient signal 404 exceeds a predetermined gradient threshold. The atmospheric pressure level may be used to determine a zero level of pressure for other calculations.

The control circuit takes into account asymmetric inhalation / exhalation airway resistance and generates a reasonably healthy exhalation (p> _patm ) and an exhalation signal that differs from COPD or “pipe smoking” exhalation where exhalation pressure is close to atmospheric pressure. By discrimination, the atmospheric pressure may be determined (e.g., when "pipe smoking" occurs, there is no exhalation to the inhaler, so the exhalation pressure will be close to the noise value of the pressure sensor).

The control circuit may generate an unfiltered pressure signal (not shown), for example, using the raw pressure signal and the atmospheric pressure, so that the control circuit detects the change in atmospheric pressure. Can be taken into account. The unfiltered pressure signal is sometimes called the gauge pressure. For example, the control circuit can generate an unfiltered pressure signal by subtracting the atmospheric pressure level from the raw pressure signal so that atmospheric pressure changes are taken into account when performing other calculations. Is done. Thus, the unfiltered pressure signal can be indicative of the airflow through the inhaler (eg, through the flow path of the inhaler) independent of, for example, any atmospheric pressure changes. For example, the unfiltered pressure signal can provide a gauge pressure related to flow rate by a turbulence equation (gauge pressure = (flow rate × flow resistance) ² ).

  The control circuit may generate the flow signal 402. Flow signal 402 may be a “low noise” version of the unfiltered pressure signal. Accordingly, the flow signal 402 may be a pressure signal. The control circuit averages the unfiltered pressure signal over time, applies a low-pass filter to the unfiltered pressure signal, applies an adaptive filter algorithm to the unfiltered pressure signal, The flow signal 402 may be generated by using a similar technique. For example, the control circuit may sample the unfiltered pressure signal at a sampling rate (eg, 100 Hz) to generate the flow signal 402. Accordingly, the control circuit may generate the flow signal 402 using the unfiltered pressure signal by sampling the unfiltered pressure signal over time, such that the flow signal 402 is , The average output of the unfiltered pressure signal. In some embodiments, the control circuit determines the flow signal 402 by sampling the unfiltered pressure signal while taking into account the resistance of the flow path, and samples the sample over time to determine the flow signal 402. May be added. Further, when generating the flow signal 402, the control circuit may non-linearly scale the unfiltered pressure signal with a drag coefficient associated with a flow path (eg, a suction / suction port).

  The control circuit may use the flow signal 402 (and / or the raw or unfiltered pressure signal) to determine one or more metrics. The control circuit may determine a pressure change rate (eg, gradient) signal 404 based on, for example, the flow signal 402 and time. The control circuit may determine the volume signal 406 using, for example, the flow signal 402, time, flow resistance associated with the flow path, and atmospheric pressure. The volume signal 406 may indicate the volume of air that the user moves through the mouthpiece of the inhaler. The control circuit may provide a raw pressure signal, an unfiltered pressure signal, a flow signal 402, a gradient signal 404, a volume signal 406, an atmospheric pressure (eg, an average atmospheric pressure) and / or any other signal (raw Pressure signal, unfiltered pressure signal and / or derived using flow signal 402) may be stored in memory.

  Flow signal 402 may be defined by multiple cycles, such as cycles 412A and 412B. The cycle of the flow signal 402 may include, for example, a negative pressure portion (eg, a negative gauge pressure portion) and a positive pressure portion (eg, a positive gauge pressure portion) when performing periodic breathing (eg, a pipe). If smoking is done, see only the negative part). For example, the cycle of the flow signal 402 may begin at a zero crossing where the flow signal 402 becomes negative, cross over zero, become positive, and then return to zero again (e.g., before becoming negative again thereafter). ). The negative pressure portion of the cycle of the flow signal 402 and the positive pressure portion of the same cycle of the flow signal 402 may be asymmetric (e.g., the suction may be at a different pressure than the corresponding discharge of the same flow). . For example, the positive pressure portion (eg, caused by exhalation through the inhaler) may be larger than the negative pressure portion of the cycle of the flow signal 402 (eg, caused by suction through the inhaler).

  The control circuit may include a raw pressure signal, an unfiltered pressure signal, a flow signal 402, a gradient signal 404, a volume signal 406, an atmospheric pressure reading, and / or any other signal (using the raw pressure signal). One or more of these) may be used to determine whether the user is inhaling and / or exhaling. For example, the control circuit may determine a user's successful inhalation based on the gradient signal 404, the volume signal 406, and / or the flow signal 402. Typically, a successful inhalation is characterized by, for example, a rate of pressure change greater than an environmental change (eg, an environmental change due to weather, altitude change, etc.), and a relative total volume.

  The signal 408 representing the state of the inhaler (eg, as described herein) may include steps representing various states of the inhaler. For example, 422 may correspond to the inactive / detected state of the inhalation device (eg, when the drug cartridge is connected to the body of the inhalation device; 606 of inhalation detection procedure 600 described herein). . The inhalation device may be triggered to enter 422 after the medicament cartridge is connected to the body, and may be in a non-activated, non-detected state (e.g., 602 of inhalation detection procedure 600) before that. At 422, the inhaler determines whether the gradient signal 404 is above a threshold or within a predetermined gradient range (eg, whether the rate of change of the flow signal 402 is above a threshold or within a predetermined gradient range). May be determined.

  If the inhaler determines that the gradient signal 404 is above a threshold or within a predetermined gradient range, the inhaler may be 424. 424 corresponds to the operating state of the inhaler (eg, 610 of the inhalation detection procedure 600), where the control circuit may determine whether the volume signal 406 exceeds a threshold. If the inhaler determines that the volume signal 406 exceeds the threshold, the inhaler may be at 426. 426 corresponds to the operating state of the inhaler (eg, 612 of inhalation detection procedure 600), where the control circuit may determine whether the pressure of flow signal 402 has returned to the atmospheric pressure threshold.

  If the inhaler determines that the pressure of the flow signal 402 has returned to the atmospheric pressure threshold (eg, the user has stopped inhaling and / or has started exhaling), the inhaler may become 428. At 428, the inhalation device may determine whether the slope of the flow signal (eg, the second cycle of the flow signal) is above a slope threshold or within a predetermined slope range, or the flow signal (eg, , The second cycle of the flow signal) may be determined to be above a pressure threshold (eg, 614 of the inhalation detection procedure 600). If the inhaler determines that the gradient of the flow signal exceeds the gradient threshold or is within a predetermined gradient range, and if the inhaler determines that the pressure measurement of the flow signal exceeds the pressure threshold, the inhaler will It may be 410.

  At 410, the inhaler may generate a trigger signal to control the timing of operation of the vibrating element to release the drug into the dosing chamber and return to 424 (eg, 614 and 610 of the inhalation detection procedure 600). Transition between). The inhalation device may return to state 424 until the dosing schedule is completed or until the measured value (eg, based on the flow signal 402, the gradient signal 404, and / or the volume signal 406) does not meet or exceed an associated threshold or range. You may proceed to 410. The inhaler may, for example, start a timer after 410. Upon expiration of the timer, the inhaler returns to state 422 so that the inhaler does not determine that non-respiratory atmospheric disturbances have exceeded a threshold (e.g., that non-respiratory atmospheric disturbances are not detected as inhaled. Do).

  FIG. 5 is a diagram of an example of a system 500 including the inhalation device 502. The system 500 includes an inhalation device 502, a mobile device 504, a public and / or private network 506 (eg, the Internet, a cloud network), a healthcare provider 508, and a third party 510 (eg, friends, family, pharmaceutical companies, etc.). May be included. The inhalation device 502 may be an example of the inhalation device 100 and / or the inhalation device 200. The inhalation device 502 may transfer to the mobile device 504, for example, inhalation data (eg, pressure signals, flow signals, volume signals, etc.), data generated or determined based on the inhalation data, medication information, etc. . The inhalation device 502 may receive data from the mobile device, for example, about program instructions, operating system changes, medication information, alerts or notifications, and the like.

Mobile device 504 is a smart phone (for example, iPhone ^(TM) smartphones, Android ^(TM) smartphone or Blackberry ^(R) smartphone,), a personal computer, a laptop, a wireless enabled media device (for example, MP3 players, game devices , TV, media streaming device (e.g., Amazon Fire TV, Nexus player, etc.), etc.), a tablet device (e.g., iPad ^(TM) handheld computing devices), Wi-Fi / wireless communications enabled television, or any other, It may include any suitable Internet Protocol enabled device. For example, the mobile device 504 can be a Wi-Fi communication link, a Wi-MAX communication link, a Bluetooth or Bluetooth smart communication link, a near field communication (NFC) link, a cellular communication link, a TV white space (TVWS) communication link, or a combination thereof. It may be configured to transmit and / or receive RF signals via any combination.

  Mobile device 504 may also transfer data via public and / or private network 506 to healthcare provider 508 and / or one or more third parties 510 (eg, friends, family, pharmaceutical companies, etc.). Good.

  Inhalation devices (eg, inhalation device 100, inhalation device 200, and / or inhalation device 502), for example, determine and analyze multiple signals received from pressure sensors over multiple different cycles to provide a strong estimate of human breathing. It may be configured to do so. Once the signal or measurement calculated using the signal is indicative of human respiration (eg, the signal or measurement is above a threshold, in range, etc., as described herein). If the inhalation device determines that it does, the inhalation device may prepare and deliver the medicament to the user during their natural respiratory cycle. For example, the inhaler may receive and / or determine one or more pressure measurements, such as, but not limited to, flow rate (eg, gauge pressure), rate of pressure change, volume, etc., based on the received signal. Is also good. The inhaler then determines whether the measured value has characteristics corresponding to human respiration (eg, the measured value is above a threshold, in range, etc., as described herein). May be. For example, the inhalation device may use multiple measurements in any order and combination to better ensure that the signal measured by the pressure sensor is indicative of human breathing. After determining that the measured values have characteristics corresponding to human respiration, the inhalation device confirms inhalation, prepares the blister pack, and / or generates one or more trigger signals for driving the vibrating element. You may. As a result, by using one or more measurements, the inhalation device can reduce the instances of false triggers that prepare the medication when the user is not breathing through the inhalation device. .

  For example, FIG. 6 is a flow diagram of an example of an inhalation detection procedure 600 performed by an inhaler (eg, inhaler 100, inhaler 200 and / or inhaler 502). The inhalation detection procedure 600 may begin when the power of the inhalation device is turned on. At 602, the inhaler may be in an undetected state and may not receive a pressure signal from the sensor system (e.g., whether a user is inhaling via the inhaler or exhaling into the inhaler). Not detected). For example, the inhalation device may not receive a raw pressure signal when no drug cartridge is attached to the inhalation device.

  The control circuit may use a plurality of cycles of the flow signal (eg, the flow signal 402) to determine a successful inhalation by the user and provide the user with medication. For example, the control circuit may be configured to use a first cycle of the flow signal to confirm user inhalation. The control circuit may use a subsequent (eg, second) cycle of the flow signal to advance the blister pack containing a dose of drug. The control circuit may generate a trigger signal using one or more subsequent cycles of the flow signal to cause the vibrating element to release a dose of medicament from the blister of the blister pack into the dosing chamber. .

  The inhaler may enter a detection state 604 and receive a pressure signal (eg, a raw pressure signal) from the sensor system. The inhaler may, for example, enter the detection state 604 when a drug cartridge is attached to the inhaler. At 606, the inhaler may be inactive and receiving a raw pressure signal from the sensor system. The inhaler may use the raw pressure signal to determine an atmospheric pressure measurement (eg, an average atmospheric pressure measurement) during periods of no user activity (eg, 606). The inhaler may determine the atmospheric pressure, as user inhalation operates on atmospheric pressure, which may vary according to altitude and weather conditions, for example. The inhaler may store the average atmospheric pressure measurement in a memory. The inhaler may measure and store the average atmospheric pressure while waiting for the gradient of the flow signal to exceed a predetermined gradient threshold, or may continuously measure and store the average atmospheric pressure measurement. You may.

  The inhalation device may, for example, determine the unfiltered pressure signal using the raw pressure signal and the average atmospheric pressure measurement as described herein. The inhalation device may use the unfiltered pressure signal to determine the flow signal, for example, as described herein. Thus, the flow signal can be a low noise indicator of the pressure through the flow path of the inhaler and can take into account changes in atmospheric pressure. The inhalation device may use the flow signal (eg, directly or indirectly) as a baseline to identify changes in pressure related to someone's breathing, or changes in altitude or weather conditions. In this manner, the success of inhalation may be determined using the flow signal taking the atmospheric pressure into consideration as a baseline.

  At 606, the control circuit may determine that the slope of the first cycle of the flow signal is above a predetermined slope threshold (e.g., 250 pa / sec) or within a predetermined slope range (e.g., 250-3,700 pa / sec). It may be configured to determine whether or not there is. The control circuit may use the flow signal or use a gradient signal derived using the flow signal (eg, the gradient signal 404) to determine the gradient of the first cycle. The control circuit may be configured to enter the active state 608 when the slope of the first cycle of the flow signal exceeds a predetermined slope threshold or falls within a predetermined slope range. For example, the control circuit may determine whether the flow signal indicates a pressure change rate indicative of a user inhalation (eg, expiration if a positive pressure change rate is detected).

  In the operating state 608, the control circuit may be configured to calculate an inhalation volume using a first cycle of the flow signal (and / or a volume signal such as the volume signal 406) at 610. . The suction volume may indicate a volume of air passing through a flow path of the suction device. At 610, if the control circuit determines that the first cycle suction volume is above the suction volume threshold (eg, 125 mL), the control circuit may proceed to 612. The control circuit may be configured to determine at 612 whether the pressure measurement of the first cycle of the flow signal has returned to within an atmospheric pressure threshold (eg, within 15 pa). For example, the control circuit may determine at 610 whether a volume of air has passed through the flow path of the inhaler (indicating a user inhalation). Next, the control circuit may determine that the pressure measurement is within an atmospheric pressure threshold (e.g., within an average amount of atmospheric pressure. This may indicate that the user has exhaled and that the flow signal may enter the next cycle. May be determined. Further, the control circuit may determine that the pressure measurement in the first cycle of the flow signal is large, for example, when the pressure measurement crosses a negative / positive boundary (eg, zero crossing) at the center of the first cycle of the flow signal. It can be determined that it has returned to within the atmospheric pressure threshold, which may indicate, for example, that the user has exhaled into the inhaler.

  The control circuit may be configured to determine at 614 whether the slope of the second cycle of the flow signal is above a predetermined slope threshold or within a predetermined slope range. For example, the control circuit may determine whether the slope of the flow signal (eg, a negative slope) is above or within a threshold. The control circuit may also determine, at 614, whether the pressure measurement in the second cycle of the flow signal exceeds a pressure threshold (eg, as is done for the first cycle). The control circuit determines that the slope of the second cycle of the flow signal is above or within a predetermined slope threshold, and the pressure measurement of the second cycle of the flow signal is above the pressure threshold. If so, the control circuit may generate a trigger signal to cause the vibrating element to release the medication into the dosing chamber and to the patient before returning to 610. The control circuit may repeat 610-614 until a particular dosage regimen is completed, and may continue to generate a trigger signal to cause the vibrating element to release the medication in the medication chamber and to the patient (e.g., one to more than one). Anything up to the trigger signal may be used to provide the user with the full dose of medication). If at any point during the inhalation detection procedure 600, the control circuit determines that the measured value does not exceed or does not exceed the threshold or range, the control circuit may return to 606. The control circuit may also start a timer when the operating state 608 is reached and return to 606 if the timer expires before the control circuit determines a successful inhalation.

  Judgment of inhalation using a specific pressure metric (eg, gradient, volume, etc.) and related actions based on the determination of inhalation (eg, confirmation of inhalation, preparation of blister pack, trigger signal for driving vibrating element) It should be noted that the inhaler may be configured to perform one or more operations using one or more different pressure metrics. . For example, the inhaler may determine that the first cycle of the flow signal indicates inhalation based on the slope and volume, confirm inhalation, and prepare the blister pack accordingly. Thereafter, upon determining that the second cycle of the flow signal also indicates inhalation (e.g., based on slope and volume), the inhaler generates a trigger signal to cause the electrically oscillating element to move the blister pack from the blister pack into the dosing chamber. One dose of the drug may be released. In another example, the inhaler may determine, based on the volume, that the first cycle of the flow signal indicates inhalation, and confirm inhalation accordingly. Thereafter, if it is determined that the second cycle of the flow signal is also indicative of inhalation (e.g., based on slope, volume and / or inhalation / exhalation duration characteristics that would indicate human breathing), the inspiratory The device may prepare the blister pack and generate a trigger signal to cause the motorized vibration element to release a dose of medicament from the blister pack into the dosing chamber.

  The slope of the flow signal cycle exceeds a predetermined slope threshold, and / or the suction volume of the cycle exceeds the suction volume threshold (and the pressure measurement of the flow signal cycle returns to within the atmospheric pressure threshold). Control circuit determines that the user has successfully inhaled (and exhaled (periodic breathing has been performed) via the inhalation device. Case)) may be determined. However, the control circuit may wait to trigger the release of the drug until the control circuit determines a plurality of successful inhalations. For example, the control circuit may use one or more determined successful inhalations as a check to ensure that the drug is not released upon a "false" inhalation determination. When the control circuit determines a subsequent successful inhalation, it may prepare a dose of medication, for example, by advancing the blister pack and exposing the medication in the blister to the dosing chamber. Thereafter, when the control circuit determines one or more subsequent successful inhalations (e.g., if a portion of the drug is delivered to the patient with each inhalation), the control circuit generates a trigger signal to oscillate. The device may cause release of the drug into the dosing chamber and to the patient. The control circuit may utilize a plurality of triggers to cause the oscillating element to release the drug into the dispensing chamber and to the patient, such as to accommodate short inhalation times and to prevent dispensing during exhalation. Is prevented, and the vibrating element can be cooled between operations. The control circuit may also provide a single trigger signal to the vibrating element (eg, if an entire dose is delivered to the patient in a single inhalation) to provide the vibrating element with a blister from the blister into the dosing chamber. And release of the entire drug to the patient.

Claims (16)

An inhalation device for delivering a drug to a user,
A mouthpiece, a dosing chamber, and a flow path connecting the mouthpiece to the dosing chamber, wherein the dosing chamber is configured to deliver the medicament to the user via the mouthpiece;
An electric vibration element,
A sensor system configured to generate a pressure signal indicative of airflow through the flow path;
Receiving the pressure signal from the sensor system, activating and deactivating the vibrating element, performing an inhalation detection procedure to determine a plurality of successful inhalations, and based on the plurality of successful inhalations, the electric vibrating element A controller configured to generate a trigger signal to control the timing of the operation of the device to release the drug into the dispensing chamber;
An inhalation device comprising: The pressure signal includes an absolute air pressure measurement;
The inhaler according to claim 1, wherein: The controller is further configured to generate a flow signal based on the pressure signal and the atmospheric pressure.
The inhaler according to claim 1, wherein: The controller confirms user inhalation using a first cycle of the flow signal, prepares a blister pack containing a dose of medication using a second cycle of the flow signal, and Configured to generate a trigger signal using a third cycle of the signal to cause the motorized oscillating element to release a dose of medicament from the blister pack into the dosing chamber.
The inhaler according to claim 3, characterized in that: The inhalation detection procedure is configured to determine an atmospheric pressure using the pressure signal during periods of no user activity, determine an average atmospheric pressure over time, and store the average atmospheric pressure in a memory. Including the controller,
The inhaler according to claim 3, characterized in that: The inhalation detection system determines whether a slope of a first cycle of the flow signal exceeds a predetermined slope threshold, and determines whether the slope of the first cycle of the flow signal exceeds the predetermined slope threshold. Including the controller configured to be in an active state;
In the operating state, the controller:
Calculating an inhalation volume using the first cycle of the flow signal;
Determining that the suction volume of the first cycle has exceeded a suction volume threshold,
Determining that the first cycle pressure measurement of the flow signal has returned to within an atmospheric pressure threshold;
Determining that the slope of the second cycle of the flow signal exceeds a predetermined slope threshold, and determining that the pressure measurement of the second cycle of the flow signal exceeds a pressure threshold;
Triggering a trigger signal based on the slope of the second cycle of the flow signal exceeding a predetermined slope threshold and the pressure measurement of the second cycle of the flow signal exceeding the pressure threshold. Generating and configured to cause the electrically powered vibrating element to release a drug into the dosing chamber,
The inhaler according to claim 5, characterized in that: The controller is further configured to start a timer when the operating state is reached, and to return to the inactive state when the timer expires.
The inhaler according to claim 6, characterized in that: The controller is further configured to exit the operating state when the suction volume does not exceed the suction volume threshold, or when the suction gradient does not exceed the predetermined gradient threshold.
The inhaler according to claim 6, characterized in that: The controller is further configured to calculate a volume using the pressure signal and determine a successful inhalation based on the volume being above a volume threshold.
The inhaler according to claim 1, wherein: The sensor system includes an atmospheric pressure sensor;
The inhaler according to claim 1, wherein: The sensor system includes a differential pressure sensor;
The inhaler according to claim 1, wherein: The electric vibration element is configured to vibrate or acoustically levitate the medicament from the blister into the dispensing chamber.
The inhaler according to claim 1, wherein: The dosing chamber includes a nozzle;
The electrically oscillating element is configured to excite the dosing chamber such that the drug exits the dosing chamber through the nozzle and into the flow path.
The inhaler according to claim 1, wherein: It further comprises a replaceable cartridge,
The replaceable cartridge includes the dosing chamber, the medicament, and the motorized oscillating element;
The inhaler according to claim 1, wherein: Further comprising a user interface,
The inhaler according to claim 1, wherein: Further comprising a communication circuit,
The inhaler according to claim 1, wherein:

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